tbuckley/cabot-search huggingface dataset:
Dissecting neural computations in the human auditory pathway using deep neural networks for speech
Authors: Yuanning Li, Gopala K. Anumanchipalli, Abdelrahman Mohamed, Peili Chen, Laurel H. Carney, Junfeng Lu, Jinsong Wu, Edward F. Chang
Journal: Nature Neuroscience (2023)

Abstract The human auditory system extracts rich linguistic abstractions from speech signals. Traditional approaches to understanding this complex process have used linear feature-encoding models, with limited success. Artificial neural networks excel in speech recognition tasks and offer promising computational models of speech processing. We used speech representations in state-of-the-art deep neural network (DNN) models to investigate neural coding from the auditory nerve to the speech cortex. Representations in hierarchical layers of the DNN correlated well with the neural activity throughout the ascending auditory system. Unsupervised speech models performed at least as well as other purely supervised or fine-tuned models. Deeper DNN layers were better correlated with the neural activity in the higher-order auditory cortex, with computations aligned with phonemic and syllabic structures in speech. Accordingly, DNN models trained on either English or Mandarin predicted cortical responses in native speakers of each language. These results reveal convergence between DNN model representations and the biological auditory pathway, offering new approaches for modeling neural coding in the auditory cortex.
Development and validation of an artificial intelligence model for predicting post‐transplant hepatocellular cancer recurrence
Authors: Quirino Lai, Carmine De Stefano, Jean Emond, Prashant Bhangui, Toru Ikegami, Benedikt Schaefer, Maria Hoppe‐Lotichius, Anna Mrzljak, Takashi Ito, Marco Vivarelli, Giuseppe Tisone, Salvatore Agnes, Giuseppe Maria Ettorre, Massimo Rossi, Emmanuel Tsochatzis, Chung Mau Lo, Chao‐Long Chen, Umberto Cillo, Matteo Ravaioli, Jan Paul Lerut
Journal: Cancer Communications (2023)

Development and validation of an artificial intelligence model for predicting post-transplant hepatocellular cancer recurrenceDear Editor,In recent years, criteria based on the combination of morphology and biology have been proposed for improving the selection of hepatocellular cancer (HCC) patients waiting for liver transplantation (LT) [1,2].Since all the proposed models showed suboptimal results in predicting the risk of post-LT recurrence, a prediction model constructed using artificial intelligence (AI) could be an attractive way to surpass this limit [3,4].Therefore, the Time_Radiological-response_Alpha-fetoproteIN_Artificial-Intelligence (TRAIN-AI) model was developed, combining morphology and biology tumor variables.A Training Set (n = 2,936) derived from an International Cohort was adopted to create the model.A Validation Set (n = 734) derived from the same International Cohort and an external Test Set (n = 356) were identified for internal and external validation of TRAIN-AI, respectively (Supplementary Figure S1).Training and Validation Sets presented similar characteristics (Supplementary Table S1).Conversely, relevant differences were observed when the Test Set was compared with the Validation Set; therefore, external validation of the model was performed in a very different population (i.e., Test Set) from the one from which the TRAIN-AI was derived and internally tested (i.e., Training and Validation Sets) (Supplementary Table S2). TRAIN-AI MODEL VARIABLESEight variables were significantly associated with the risk of recurrence and used for constructing the TRAIN-AI
Emerging factors affecting peri‐implant bone metabolism
Authors: Angel Insua, Pablo Galindo‐Moreno, Richard J. Miron, Hom‐Lay Wang, Alberto Monje
Journal: Periodontology 2000 (2023)

Abstract Implant dentistry has evolved to the point that standard implant osseointegration is predictable. This is attributed in part to the advancements in material sciences that have led toward improvements in implant surface technology and characteristics. Nonetheless, there remain several cases where implant therapy fails (specifically at early time points), most commonly attributed to factors affecting bone metabolism. Among these patients, smokers are known to have impaired bone metabolism and thus be subject to higher risks of early implant failure and/or late complications related to the stability of the peri‐implant bone and mucosal tissues. Notably, however, emerging data have unveiled other critical factors affecting osseointegration, namely, those related to the metabolism of bone tissues. The aim of this review is to shed light on the effects of implant‐related factors, like implant surface or titanium particle release; surgical‐related factors, like osseodensification or implanted biomaterials; various drugs, like selective serotonin reuptake inhibitors, proton pump inhibitors, anti‐hypertensives, nonsteroidal anti‐inflammatory medication, and statins, and host‐related factors, like smoking, diet, and metabolic syndrome on bone metabolism, and aseptic peri‐implant bone loss. Despite the infectious nature of peri‐implant biological complications, these factors must be surveyed for the effective prevention and management of peri‐implantitis.
The utilization and impact of cardiovascular specialists on guideline‐directed medical scores: An analysis of a diverse, multi‐state, electronic health record‐based registry
Authors: Trejeeve Martyn, Joshua Saef, Umesh N. Khot, Kathryn A. Martinez, Todd J. Brophy, Lucianne West, Cari Cristiani, Hunter Block‐Beach, Jessica A. Hohman, Tim Sobol, Jeremy A. Brooksbank, Michael B. Surratt, Christopher Babiuch, Samir R. Kapadia, W.H. Wilson Tang, Jerry D. Estep, Randall C. Starling
Journal: European Journal of Heart Failure (2023)
Extracting immunological and clinical heterogeneity across autoimmune rheumatic diseases by cohort-wide immunophenotyping
Authors: Hiroaki Tanaka, Yukinori Okada, Shingo Nakayamada, Yusuke Miyazaki, Kyuto Sonehara, Shinichi Namba, Suguru Honda, Yuya Shirai, Kenichi Yamamoto, Satoshi Kubo, Katsunori Ikari, Masayoshi Harigai, Koshiro Sonomoto, Yoshiya Tanaka
Journal: Annals of the Rheumatic Diseases (2023)

Extracting immunological and clinical heterogeneity across autoimmune rheumatic diseases (AIRDs) is essential towards personalised medicine.
Longitudinal evaluation of the biodistribution and cellular internalization of the bispecific CD3xTRP1 antibody in syngeneic mouse tumor models
Authors: Gerwin Gerhard Wemke Sandker, Jim Middelburg, Evienne Wilbrink, Janneke Molkenboer-Kuenen, Erik Aarntzen, Thorbald van Hall, Sandra Heskamp
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background CD3 bispecific antibodies (CD3-bsAbs) require binding of both a tumor-associated surface antigen and CD3 for their immunotherapeutic effect. Their efficacy is, therefore, influenced by the tumor uptake and the extracellular dose. To optimize their currently limited efficacy in solid tumors, increased understanding of their pharmacokinetics and in vivo internalization is needed. Methods Here, were studied the pharmacokinetics and in vivo internalization of CD3xTRP1, a fully murine Fc-inert bsAb, in endogenous TRP1-expressing immunocompetent male C57BL/6J mice bearing TRP1-positive and negative tumors over time. Matching bsAbs lacking TRP1-binding or CD3-binding capacity served as controls. BsAbs were radiolabeled with 111 In to investigate their pharmacokinetics, target binding, and biodistribution through SPECT/CT imaging and ex vivo biodistribution analyses. Co-injection of 111 In- and 125 I-labeled bsAb was performed to investigate the in vivo internalization by comparing tissue concentrations of cellular residing 111 In versus effluxing 125 I. Antitumor therapy effects were evaluated by monitoring tumor growth and immunohistochemistry. Results SPECT/CT and biodistribution analyses showed that CD3xTRP1 specifically targeted TRP1-positive tumors and CD3-rich lymphoid organ and uptake peaked 24 hours pi (KPC3-TRP1: 37.7%ID/g±5.3%ID/g, spleen: 29.0%ID/g±3.9%ID/g). Studies with control bsAbs demonstrated that uptake of CD3xTRP1 in TRP1-positive tumors and CD3-rich tissues was primarily receptor-mediated. Together with CD3xTRP1 in the circulation being mainly unattached, this indicates that CD3 + T cells are generally not traffickers of CD3-bsAbs to the tumor. Additionally, target-mediated clearance by TRP1-expressing melanocytes was not observed. We further demonstrated rapid internalization of CD3xTRP1 in KPC3-TRP1 tumors (24 hours pi: 54.9%±2.3% internalized) and CD3-rich tissues (spleen, 24 hours pi: 79.7%±0.9% internalized). Therapeutic effects by CD3xTRP1 were observed for TRP1-positive tumors and consisted of high tumor influx of CD8 + T cells and neutrophils, which corresponded with increased necrosis and growth delay. Conclusions We show that CD3xTRP1 efficiently targets TRP1-positive tumors and CD3-rich tissues primarily through receptor-mediated targeting. We further demonstrate rapid receptor-mediated internalization of CD3xTRP1 in TRP1-positive tumors and CD3-rich tissues. Even though this significantly decreases the therapeutical available dose, CD3xTRP1 still induced effective antitumor T-cell responses and inhibited tumor growth. Together, our data on the pharmacokinetics and mechanism of action of CD3xTRP1 pave the way for further optimization of CD3-bsAb therapies.
Dementia incidence trend in England and Wales, 2002–19, and projection for dementia burden to 2040: analysis of data from the English Longitudinal Study of Ageing
Authors: Yuntao Chen, Piotr Bandosz, George Stoye, Yuyang Liu, Yanjuan Wu, Sophia Lobanov-Rostovsky, Eric French, Mika Kivimaki, Gill Livingston, Jing Liao, Eric J Brunner
Journal: The Lancet Public Health (2023)

Dementia incidence declined in many high-income countries in the 2000s, but evidence on the post-2010 trend is scarce. We aimed to analyse the temporal trend in England and Wales between 2002 and 2019, considering bias and non-linearity.
Research Recommendations for Selected IARC-Classified Agents: Impact and Lessons Learned
Authors: Michelle C. Turner, Vincent Cogliano, Kathryn Guyton, Federica Madia, Kurt Straif, Elizabeth M. Ward, Mary K. Schubauer-Berigan
Journal: Environmental Health Perspectives (2023)

The International Agency for Research on Cancer (IARC) Monographs program assembles expert working groups who publish a critical review and evaluation of data on agents of interest. These comprehensive reviews provide a unique opportunity to identify research needs to address classification uncertainties. A multidisciplinary expert review and workshop held in 2009 identified research gaps and needs for 20 priority occupational chemicals, metals, dusts, and physical agents, with the goal of stimulating advances in epidemiological studies of cancer and carcinogen mechanisms. Overarching issues were also described.
Enhancing Craniofacial Bone Reconstruction with Clinically Applicable 3D Bioprinted Constructs
Authors: Hyeongjin Lee, Carlos Kengla, Han Su Kim, Ickhee Kim, Jae‐Gu Cho, Eric Renteria, Kyungsup Shin, Anthony Atala, James J. Yoo, Sang Jin Lee
Journal: Advanced Healthcare Materials (2023)

Abstract Medical imaging and 3D bioprinting can be used to create patient‐specific bone scaffolds with complex shapes and controlled inner architectures. This study investigated the effectiveness of a biomimetic approach to scaffold design by employing geometric control. The biomimetic scaffold with a dense external layer showed improved bone regeneration compared to the control scaffold. New bone filled the defected region in the biomimetic scaffolds, while the control scaffolds only presented new bone at the boundary. Histological examination also shows effective bone regeneration in the biomimetic scaffolds, while fibrotic tissue ingrowth is observed in the control scaffolds. These findings suggest that the biomimetic bone scaffold, designed to minimize competition for fibrotic tissue formation in the bony defect, can enhance bone regeneration. This study underscores the notion that patient‐specific anatomy can be accurately translated into a 3D bioprinting strategy through medical imaging, leading to the fabrication of constructs with significant clinical relevance.
Survival Among Veterans Receiving Steroids for Immune-Related Adverse Events After Immune Checkpoint Inhibitor Therapy
Authors: Inga Van Buren, Cecelia Madison, Aimee Kohn, Elizabeth Berry, Rajan P. Kulkarni, Reid F. Thompson
Journal: JAMA Network Open (2023)

Systemic steroids are commonly used to manage immune-related adverse events (irAEs), but it remains unclear whether they may undermine immune checkpoint inhibitor (ICI) therapy outcomes. Few studies have assessed the impact of steroid timing and its association with continuation or cessation of ICI therapy.
Epigenetic regulation in lung cancer
Authors: Shahin Ramazi, Maedeh Dadzadi, Zahra Sahafnejad, Abdollah Allahverdi
Journal: MedComm (2023)

Lung cancer is indeed a major cause of cancer-related deaths worldwide. The development of tumors involves a complex interplay of genetic, epigenetic, and environmental factors. Epigenetic mechanisms, including DNA methylation (DNAm), histone modifications, and microRNA expression, play a crucial role in this process. Changes in DNAm patterns can lead to the silencing of important genes involved in cellular functions, contributing to the development and progression of lung cancer. MicroRNAs and exosomes have also emerged as reliable biomarkers for lung cancer. They can provide valuable information about early diagnosis and treatment assessment. In particular, abnormal hypermethylation of gene promoters and its effects on tumorigenesis, as well as its roles in the Wnt signaling pathway, have been extensively studied. Epigenetic drugs have shown promise in the treatment of lung cancer. These drugs target the aberrant epigenetic modifications that are involved in the development and progression of the disease. Several factors have been identified as drug targets in non-small cell lung cancer. Recently, combination therapy has been discussed as a successful strategy for overcoming drug resistance. Overall, understanding the role of epigenetic mechanisms and their targeting through drugs is an important area of research in lung cancer treatment.
Recommendations for Improving Systemic Lupus Erythematosus Care From Black Adults
Authors: Bhaavna Yalavarthi, Johari Summerville, Nikki Farahani, Lillian Z. Xiao, Christine Yu, Deena Aboul-Hassan, Sia Rajgarhia, Daniel J. Clauw, J. Michelle Kahlenberg, Melissa DeJonckheere, Rachel S. Bergmans
Journal: JAMA Network Open (2023)

Importance Racial inequities in incidence, morbidity, and mortality are a defining feature of systemic lupus erythematosus (SLE). Health care systems are integral to addressing these inequities. However, qualitative evidence that highlights Black SLE care experiences is limited. Objective To identify opportunities for improving SLE care based on the experiences and perspectives of Black adults with SLE. Design, Setting, and Participants In this qualitative study, an interpretive description approach was used and data were analyzed using inductive thematic analysis. Semistructured interviews with Black adults in Michigan who were diagnosed with SLE were conducted. Interviews occurred from November 2, 2021, to July 19, 2022, and data analysis occurred from May 6, 2022, to April 12, 2023. Main Outcomes and Measures Deidentified transcripts from the interviews were analyzed to develop themes that focused on opportunities to improve quality of care and symptom management. Results The participants included 30 Black adults with SLE (97% women; mean age, 41 years; range, 18-65 years). Four main themes were identified: (1) awareness of SLE signs and symptoms before diagnosis (participants emphasized delays in diagnosis and how knowledge concerning SLE could be limited in their families and communities); (2) patient-clinician interactions (participants faced discrimination in health care settings and talked about the value of coordinated and supportive health care teams); (3) medication adherence and health effects (participants experienced a range of adverse effects from medications that treat SLE and described how monitoring medication use and efficacy could inform tailored care approaches); and (4) comprehensive care plans after diagnosis (participants reported persistent pain and other symptoms despite treatment). In the context of disease management, participants emphasized the importance of behavioral change and the negative impact of social risk factors. Conclusions and Relevance The findings of this qualitative study suggest how limited information about SLE, experiences of racism, treatment regimens, and social risk factors may affect Black people with SLE. Future research should further engage and include Black communities within the context of treatment and intervention development to reduce racial inequities.
Masks During Pandemics Caused by Respiratory Pathogens—Evidence and Implications for Action
Authors: Shama Cash-Goldwasser, Arthur L. Reingold, Stephen P. Luby, Lisa A. Jackson, Thomas R. Frieden
Journal: JAMA Network Open (2023)

As demonstrated by the influenza virus and SARS-CoV-2, viruses spread by the respiratory route can cause deadly pandemics, and face masks can reduce the spread of these pathogens. The effectiveness of responses to future epidemics and pandemics will depend at least in part on whether evidence on masks, including from the COVID-19 pandemic, is utilized.Well-designed observational studies have demonstrated the association of mask use with reduced transmission of SARS-CoV-2 in community settings, and rigorous evaluations of mask mandates have found substantial protection. Disagreement about whether face masks reduce the spread of SARS-CoV-2 has been exacerbated by a focus on randomized trials, which are limited in number, scope, and statistical power. Many effective public health policies have never been assessed in randomized clinical trials; such trials are not the gold standard of evidence for the efficacy of all interventions. Masking in the community to reduce the spread of SARS-CoV-2 is supported by robust evidence from diverse settings and populations. Data on the epidemiologic, environmental, and mask design parameters that influence the effectiveness of masking provide insights on when and how masks should be used to prevent transmission.During the next epidemic or pandemic caused by a respiratory pathogen, decision-makers will need to rely on existing evidence as they implement interventions. High-quality studies have shown that use of face masks in the community is associated with reduced transmission of SARS-CoV-2 and is likely to be an important component of an effective response to a future respiratory threat.
Natural Selection Signatures in the Hondo and Ryukyu Japanese Subpopulations
Authors: Xiaoxi Liu, Masatoshi Matsunami, Momoko Horikoshi, Shuji Ito, Yuki Ishikawa, Kunihiko Suzuki, Yukihide Momozawa, Shumpei Niida, Ryosuke Kimura, Kouichi Ozaki, Shiro Maeda, Minako Imamura, Chikashi Terao
Journal: Molecular Biology and Evolution (2023)

Natural selection signatures across Japanese subpopulations are under-explored. Here we conducted genome-wide selection scans with 622,926 single nucleotide polymorphisms for 20,366 Japanese individuals, who were recruited from the main-islands of Japanese Archipelago (Hondo) and the Ryukyu Archipelago (Ryukyu), representing two major Japanese subpopulations. The integrated haplotype score (iHS) analysis identified several signals in one or both subpopulations. We found a novel candidate locus at IKZF2, especially in Ryukyu. Significant signals were observed in the major histocompatibility complex region in both subpopulations. The lead variants differed and demonstrated substantial allele frequency differences between Hondo and Ryukyu. The lead variant in Hondo tags HLA-A*33:03-C*14:03-B*44:03-DRB1*13:02-DQB1*06:04-DPB1*04:01, a haplotype specific to Japanese and Korean. While in Ryukyu, the lead variant tags DRB1*15:01-DQB1*06:02, which had been recognized as a genetic risk factor for narcolepsy. In contrast, it is reported to confer protective effects against type 1 diabetes and human T lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis. The FastSMC analysis identified 8 loci potentially affected by selection within the past 20-150 generations, including 2 novel candidate loci. The analysis also showed differences in selection patterns of ALDH2 between Hondo and Ryukyu, a gene recognized to be specifically targeted by selection in East Asian. In summary, our study provided insights into the selection signatures within the Japanese and nominated potential sources of selection pressure.
Disparities in Continuous Glucose Monitor Use Between Children With Type 1 Diabetes Living in Urban and Rural Areas
Authors: Daniel R. Tilden, Benjamin French, Karishma A. Datye, Sarah S. Jaser
Journal: Diabetes Care (2023)

OBJECTIVE Despite evidence that continuous glucose monitoring (CGM) use is associated with lower HbA1c among children with type 1 diabetes, uptake of this technology remains lower among those with difficulty accessing health care, including those from lower socioeconomic status backgrounds and racial and ethnic minorities. In this study, we sought to explore the impact of rural location in use of CGM technology to guide patient and provider decision making. RESEARCH DESIGN AND METHODS In this retrospective study of electronic health record demographic and visits data from a single diabetes program from 1 January 2018 through 31 December 2021, we compared the odds of completing a visit with (+) and without (−) CGM interpretation between rural-urban commuting area (RUCA) designations. RESULTS Among the 13,645 visits completed by 2,008 patients with type 1 diabetes younger than age 18 years, we found children living in small rural towns had 31% lower odds (6.3% of CGM+ visits, 8.6% of CGM− visits; adjusted odds ratio [aOR] 0.69, 95% CI 0.51–0.94) and those living in isolated rural towns had 49% lower odds (2.0% of CGM+ visits, 3.4% of CGM− visits; aOR 0.51, 95% CI 0.28–0.92) of completing a CGM-billed clinic visit compared with those living in urban areas (70.0% of CGM+ visits, 67.2% of CGM− visits). We also found significant differences in CGM-billed visits by neighborhood deprivation as well as race/ethnicity and insurance payor. CONCLUSIONS Geographic location presents a meaningful barrier to access to care for patients living with type 1 diabetes. Further work is needed to identify and address the needs of children and families living in rural areas to improve the care of these patients.
Skin ageing and topical rejuvenation strategies
Authors: Tamara W Griffiths, Rachel E B Watson, Abigail K Langton
Journal: British Journal of Dermatology (2023)

Skin ageing is a complex process involving the additive effects of skin's interaction with its external environment, predominantly chronic sun exposure, upon a background of time-dependent intrinsic ageing. Skin health and beauty is considered one of the principal factors perceived to represent overall 'health and wellbeing'; thus, the demand for skin rejuvenation strategies has rapidly increased, with a worldwide annual expenditure expected to grow from $US24.6 billion to around $US44.5 billion by 2030 (https://www.databridgemarketresearch.com/reports/global-facial-rejuvenation-market). Skin rejuvenation can be achieved in several ways, ranging from laser and device-based treatments to chemical peels and injectables; however, topical skin care regimes are a mainstay treatment for ageing skin and all patients seeking skin rejuvenation can benefit from this relatively low-risk intervention. While the most efficacious topical rejuvenation treatment is application of tretinoin (all-trans retinoic acid) - a prescription-only medicine considered to be the clinical 'gold standard' - a hybrid category of 'cosmeceutical' products at the midpoint of the spectrum of cosmetics and pharmaceutical has emerged. This article reviews the clinical manifestations of skin ageing and the available topical treatments for skin rejuvenation, including retinoids, peptides and antioxidants.